Subunit-specific enhancement of glutamate receptor responses by zinc

A comparison of the effects of zinc ions on the response of two similar homomeric glutamate receptors, GluR1 and GluR3, was carried out using the Xenopus oocyte expression system. Two to 5 days after injection of the corresponding cRNA into oocytes, two-electrode voltage-clamp studies were done using primarily kainate as the glutamate agonist. Kainate produced stable responses that could be modulated by co-application of zinc. GluR3 but not GluR1 receptors produced currents that were enhanced by low concentrations of Zn2+. This Zn2+ sensitivity occurred over a narrow concentration range of 4 to 7.5 microM. Additionally, heteromeric expression of GluR3 with GluR2 and GluR1 with GluR2 both resulted in no Zn2+ potentiation. The zinc-induced enhancement of GluR3 current was not mediated by a change in sensitivity to agonist as the kainate concentration-response curve was unaltered by Zn2+. The kainate current-voltage (I-V) relationship for inward current showed a general increase in slope with little change in rectification. While there was no change in reversal potential, outward rectification became more pronounced during Zn2+ exposure. Although Ca2+ removal strongly affects the outward rectification of the I-V, the zinc-induced enhancement of GluR3 current still occurred in Ca(2+)-free saline. The major change in the kainate I-V relationship for GluR3 produced by Zn2+ may begin to explain the differential action of Zn2+ on two otherwise similar glutamate receptors. Because Zn2+ is co-released along with neurotransmitter, the differential sensitivity may be physiologically pertinent.